2. Academic Validation
  3. Computational-experimental study reveals direct target and bioactives of Ajania fruticulosa against NAFLD via TLR2/NF-κB/PPAR-γ signaling

Computational-experimental study reveals direct target and bioactives of Ajania fruticulosa against NAFLD via TLR2/NF-κB/PPAR-γ signaling

  • NPJ Sci Food. 2026 Jan 23;10(1):73. doi: 10.1038/s41538-026-00722-w.
Chaoyue Chen # 1,  Lisha Ma # 1,  Awaguli Dawuti # 1,  Xin Feng 1,  Shujie Chen 1,  Xueyan An 1,  Yulan Bai 1,  Tianfeng Zhang 1,  Mamatjan Aydin 2,  Kashif Kashmiri 1,  Zhancang Ma 3,  Wei Zhang 1,  Saimijiang Yaermaimaiti 1,  Abudumijiti Abulizi 4
Affiliations

Affiliations

  • 1 Pharmacy College of Shihezi University/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education/Collaborative Innovation Center for Efficient Safflower Production and Resource Utilization of XPCC/Institute for Safflower Industry Research, Shihezi University, Shihezi, China.
  • 2 Uyghur Medicines Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, China.
  • 3 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, China.
  • 4 Pharmacy College of Shihezi University/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education/Collaborative Innovation Center for Efficient Safflower Production and Resource Utilization of XPCC/Institute for Safflower Industry Research, Shihezi University, Shihezi, China. [email protected].
  • # Contributed equally.
PMID: 41577727 DOI: 10.1038/s41538-026-00722-w
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with limited treatment options. This study investigated the therapeutic potential of water extract of Ajania fruticulosa (WEAF) against NAFLD in cellular and animal models. WEAF significantly attenuated obesity, lipid accumulation, liver injury, and inflammation in NAFLD mice. Next, UPLC-MS/MS-based network pharmacology and Molecular Biology revealed that WEAF alleviated NAFLD by TLR2-mediated MyD88/NF-κB and SREBP1/PPAR-γ pathways, with 3,4-dihydroxyphenylpropionic acid, glycitein, and isorhapontigenin identified as the primary bioactive compounds. Finally, molecular docking, molecular dynamics, drug affinity responsive target stability, and cellular thermal shift assay confirmed that glycitein and isorhapontigenin directly bind to TLR2 to modulate the NF-κB/PPAR-γ signaling, and their anti-NAFLD effects were abolished by TLR2 Agonist Pam3CSK4. In conclusion, WEAF and its key active compounds, glycitein and isorhapontigenin, effectively ameliorate obesity-induced NAFLD via the NF-κB/PPAR-γ signaling pathway by targeting TLR2, supporting their potential as therapeutic target and agents for NAFLD.

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